Theta Burst Transcranial Magnetic Stimulation Research Articles

Augmentation of fear extinction by theta-burst transcranial magnetic stimulation of the prefrontal cortex in humans.

BackgroundFear extinction alone does not erase the original fear memory. Interventions that enhance extinction can be beneficial for the treatment of fear-related disorders. Repetitive transcranial magnetic stimulation has been shown to improve memory performance. The present study examined the effects of intermittent theta-burst stimulation (iTBS) on fear extinction and the return of fear memory in humans.MethodsNinety-one young healthy volunteers underwent 3 experiments using a randomized controlled experimental design. Participants first acquired fear conditioning, after which they received 30 Hz iTBS before and after extinction training. The iTBS was applied to 1 of 2 targets: the left dorsolateral prefrontal cortex (dlPFC) and the vertex (control). Fear responses were measured 24 hours later and 1 month later.ResultsDuring the spontaneous recovery and reinstatement tests, iTBS of the left dlPFC before and after extinction significantly reduced fear response, whereas iTBS of the vertex had no effect on fear memory performance. This combined approach had a relatively long-lasting effect (i.e., at least 1 month).LimitationsWe did not explore the effect of iTBS of the dlPFC on the expression of fear without extinction training. The neural mechanisms of iTBS with fear extinction to inhibit the fear response are unclear. Our results are preliminary and should be interpreted with caution.ConclusionThe present results showed that 30 Hz iTBS of the left dlPFC enhanced retention of fear extinction. Our study introduces a new intervention for fear memory and suggests that the left dlPFC may be a treatment target for fear-related disorders.

Efficacy of Active vs Sham Intermittent Theta Burst Transcranial Magnetic Stimulation for Patients With Bipolar Depression

Major depressive episodes in bipolar disorder are common and debilitating. Repetitive transcranial magnetic stimulation is well established in the treatment of major depressive disorder, and the intermittent theta burst stimulation (iTBS) protocol is replacing conventional protocols because of noninferiority and reduced delivery time. However, iTBS has not been adequately studied in bipolar disorder and, therefore, its efficacy is uncertain. To determine whether iTBS to the left dorsolateral prefrontal cortex (LDLPFC) is safe and efficacious in the treatment of acute bipolar depression. This study was a double-blind, 4-week, randomized clinical trial of iTBS targeting the LDLPFC. Two Canadian academic centers recruited patients between 2016 and 2020. Adults with bipolar disorder type I or type II experiencing an acute major depressive episode were eligible if they had not benefited from a first-line treatment for acute bipolar depression recommended by the Canadian Network for Mood and Anxiety Treatments and were currently treated with a mood stabilizer, an atypical antipsychotic, or their combination. Seventy-one participants were assessed for eligibility, and 37 were randomized to daily sham iTBS or active iTBS using a random number sequence, stratified according to current pharmacotherapy. Data analysis was performed from April to September 2020. Four weeks of daily active iTBS (120% resting motor threshold) or sham iTBS to the LDLPFC. Nonresponders were eligible for 4 weeks of open-label iTBS. The primary outcome was the change in score on the Montgomery-Asberg Depression Rating Scale from baseline to study end. Secondary outcomes included clinical response, remission, and treatment-emergent mania or hypomania. The trial was terminated for futility after 37 participants (23 women [62%]; mean [SD] age, 43.86 [13.87] years; age range, 20-68 years) were randomized, 19 to sham iTBS and 18 to active iTBS. There were no significant differences in Montgomery-Asberg Depression Rating Scale score changes (least squares mean difference between groups, -1.36 [95% CI, -8.92 to 6.19; P = .91] in favor of sham iTBS), and rates of clinical response were low in both the double-blind phase (3 of 19 participants [15.8%] in the sham iTBS group and 3 of 18 participants [16.7%] in the active iTBS group) and open-label phase (5 of 21 participants [23.8%]). One active iTBS participant had a treatment emergent hypomania, and a second episode occurred during open-label treatment. iTBS targeting the LDLPFC is not efficacious in the treatment of acute bipolar depression in patients receiving antimanic or mood stabilizing agents. Additional research is required to understand how transcranial magnetic stimulation treatment protocols differ in efficacy between unipolar and bipolar depression. ClinicalTrials.gov Identifier: NCT02749006.

Differences in brain structure and theta burst stimulation-induced plasticity implicate the corticomotor system in loss of function after musculoskeletal injury.

Traumatic musculoskeletal injury (MSI) may involve changes in corticomotor structure and function, but direct evidence is needed. To determine the corticomotor basis of MSI, we examined interactions among skeletomotor function, corticospinal excitability, corticomotor structure (cortical thickness and white matter microstructure), and intermittent theta burst stimulation (iTBS)-induced plasticity. Nine women with unilateral anterior cruciate ligament rupture (ACL) 3.2 ± 1.1 yr prior to the study and 11 matched controls (CON) completed an MRI session followed by an offline plasticity-probing protocol using a randomized, sham-controlled, double-blind, cross-over study design. iTBS was applied to the injured (ACL) or nondominant (CON) motor cortex leg representation (M1LEG) with plasticity assessed based on changes in skeletomotor function and corticospinal excitability compared with sham iTBS. The results showed persistent loss of function in the injured quadriceps, compensatory adaptations in the uninjured quadriceps and both hamstrings, and injury-specific increases in corticospinal excitability. Injury was associated with lateralized reductions in paracentral lobule thickness, greater centrality of nonleg corticomotor regions, and increased primary somatosensory cortex leg area inefficiency and eccentricity. Individual responses to iTBS were consistent with the principles of homeostatic metaplasticity; corresponded to injury-related differences in skeletomotor function, corticospinal excitability, and corticomotor structure; and suggested that corticomotor adaptations involve both hemispheres. Moreover, iTBS normalized skeletomotor function and corticospinal excitability in ACL. The results of this investigation directly confirm corticomotor involvement in chronic loss of function after traumatic MSI, emphasize the sensitivity of the corticomotor system to skeletomotor events and behaviors, and raise the possibility that brain-targeted therapies could improve recovery.NEW & NOTEWORTHY Traumatic musculoskeletal injuries may involve adaptive changes in the brain that contribute to loss of function. Our combination of neuroimaging and theta burst transcranial magnetic stimulation (iTBS) revealed distinct patterns of iTBS-induced plasticity that normalized differences in muscle and brain function evident years after unilateral knee ligament rupture. Individual responses to iTBS corresponded to injury-specific differences in brain structure and physiological activity, depended on skeletomotor deficit severity, and suggested that corticomotor adaptations involve both hemispheres.

Intermittent theta burst stimulation for negative symptoms of schizophrenia\u2014A double-blind, sham-controlled pilot study

Optimal noninvasive brain stimulation parameters for the treatment of negative symptoms of schizophrenia remain unclear. Here, we aimed to investigate the clinical and biological effects of intermittent theta burst transcranial magnetic stimulation (iTBS) in patients with treatment-resistant negative symptoms of schizophrenia (NCT00875498). In a randomized sham-controlled 2-arm study, 22 patients with schizophrenia and treatment-resistant negative symptoms received 20 sessions of either active (n = 12) or sham (n = 10) iTBS. Sessions were delivered twice a day on 10 consecutive working days. Negative symptom severity was assessed 5 times using the Scale for the Assessment of Negative Symptoms (SANS): before iTBS, after iTBS, and 1, 3, and 6 months after iTBS. As a secondary objective, we explored the acute effects of iTBS on functional connectivity of the left dorsolateral prefrontal cortex (DLPFC) using seed-based resting-state functional connectivity MRI (rsFC fMRI) images acquired before and after iTBS. Active iTBS over the left DLPFC significantly decreased negative symptoms severity compared to sham iTBS (F(3,60) = 3.321, p = 0.026). Post hoc analyses revealed that the difference between groups was significant 6 months after the end of stimulation sessions. Neuroimaging revealed an increase in rsFC between the left DLPFC and a brain region encompassing the right lateral occipital cortex and right angular gyrus and a right midbrain region that may encompass dopamine neuron cell bodies. Thus, iTBS over the left DLPFC can alleviate negative symptoms of schizophrenia. The effect might be driven by significant modulation of dopamine transmission.

Visual cortex cTBS increases mixed percept duration while a-tDCS has no effect on binocular rivalry.

Neuromodulation of the primary visual cortex using anodal transcranial direct current stimulation (a-tDCS) can alter visual perception and enhance neuroplasticity. However, the mechanisms that underpin these effects are currently unknown. When applied to the motor cortex, a-tDCS reduces the concentration of the inhibitory neurotransmitter gamma aminobutyric acid (GABA), an effect that has been linked to increased neuroplasticity. The aim of this study was to assess whether a-tDCS also reduces GABA-mediated inhibition when applied to the human visual cortex. Changes in visual cortex inhibition were measured using the mixed percept duration in binocular rivalry. Binocular rivalry mixed percept duration has recently been advocated as a direct and sensitive measure of visual cortex inhibition whereby GABA agonists decrease mixed percept durations and agonists of the excitatory neurotransmitter acetylcholine (ACH) increase them. Our hypothesis was that visual cortex a-tDCS would increase mixed percept duration by reducing GABA-mediated inhibition and increasing cortical excitation. In addition, we measured the effect of continuous theta-burst transcranial magnetic stimulation (cTBS) of the visual cortex on binocular rivalry dynamics. When applied to the motor or visual cortex, cTBS increases GABA concentration and we therefore hypothesized that visual cortex cTBS would decrease the mixed percept duration. Binocular rivalry dynamics were recorded before and after active and sham a-tDCS (N = 15) or cTBS (N = 15). Contrary to our hypotheses, a-tDCS had no effect, whereas cTBS increased mixed percepts during rivalry. These results suggest that the neurochemical mechanisms of a-tDCS may differ between the motor and visual cortices.

Theta-burst TMS of lateral occipital cortex reduces BOLD responses across category-selective areas in ventral temporal cortex

Human visual cortex contains three scene-selective regions in the lateral, medial and ventral cortex, termed the occipital place area (OPA), medial place area (MPA) and parahippocampal place area (PPA). Using functional magnetic resonance imaging (fMRI), all three regions respond more strongly when viewing visual scenes compared with isolated objects or faces. To determine how these regions are functionally and causally connected, we applied transcranial magnetic stimulation to OPA and measured fMRI responses before and after stimulation, using a theta-burst paradigm (TBS). To test for stimulus category-selectivity, we presented a range of visual categories (scenes, buildings, objects, faces). To test for specificity of any effects to TBS of OPA we employed two control conditions: Sham, with no TBS stimulation, and an active TBS-control with TBS to a proximal face-selective cortical region (occipital face area, or OFA). We predicted that TBS to OPA (but not OFA) would lead to decreased responses to scenes and buildings (but not other categories) in other scene-selective cortical regions. Across both ROI and whole-volume analyses, we observed decreased responses to scenes in PPA as a result of TBS. However, these effects were neither category specific, with decreased responses to all stimulus categories, nor limited to scene-selective regions, with decreases also observed in face-selective fusiform face area (FFA). Furthermore, similar effects were observed with TBS to OFA, thus effects were not specific to the stimulation site in the lateral occipital cortex. Whilst these data are suggestive of a causal, but non-specific relationship between lateral occipital and ventral temporal cortex, we discuss several factors that could have underpinned this result, such as the differences between TBS and online TMS, the role of anatomical distance between stimulated regions and how TMS effects are operationalised. Furthermore, our findings highlight the importance of active control conditions in brain stimulation experiments to accurately assess functional and causal connectivity between specific brain regions.

Transcranial magnetic stimulation for post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder. While current treatment options are effective for some, many individuals fail to respond to first-line psychotherapies and pharmacotherapy. Transcranial magnetic stimulation (TMS) has emerged over the past several decades as a noninvasive neuromodulatory intervention for psychiatric disorders including depression, with mounting evidence for its safety, tolerability, and efficacy in treating PTSD. While several meta-analyses of TMS for PTSD have been published to date showing large effect sizes on PTSD overall, there is marked variability between studies, making it difficult to draw simple conclusions about how best to treat patients. The following review summarizes over 20 years of the existing literature on TMS as a PTSD treatment, and includes nine randomized controlled trials and many other prospective studies of TMS monotherapy, as well as five randomized controlled trials investigating TMS combined with psychotherapy. While the majority of studies utilize repetitive TMS targeted to the right dorsolateral prefrontal cortex (DLPFC) at low frequency (1 Hz) or high frequency (10 or 20 Hz), others have used alternative frequencies, targeted other regions (most commonly the left DLPFC), or trialed different stimulation protocols utilizing newer TMS modalities such as synchronized TMS and theta-burst TMS (TBS). Although it is encouraging that positive outcomes have been shown, there is a paucity of studies directly comparing available approaches. Biomarkers, such as functional imaging and electroencephalography, were seldomly incorporated yet remain crucial for advancing our knowledge of how to predict and monitor treatment response and for understanding mechanism of action of TMS in this population. Effects on PTSD are often sustained for up to 2–3 months, but more long-term studies are needed in order to understand and predict duration of response. In short, while TMS appears safe and effective for PTSD, important steps are needed to operationalize optimal approaches for patients suffering from this disorder.

Callosal anisotropy predicts attentional network changes after parietal inhibitory stimulation

Hemispatial neglect is thought to result from disruption of interhemispheric equilibrium. Right hemisphere lesions deactivate the right frontoparietal network and hyperactivate the left via release from interhemispheric inhibition. Support for this putative mechanism comes from neuropsychological evidence as well as transcranial magnetic stimulation (TMS) studies in healthy subjects, in whom right posterior parietal cortex (PPC) inhibition causes neglect-like, rightward, visuospatial bias. Concurrent TMS and fMRI after right PPC TMS show task-dependent changes but may fail to identify effects of stimulation in areas not directly activated by the specific task, complicating interpretations. We used resting-state functional connectivity (RSFC) after inhibitory TMS over the right PPC to examine changes in the networks underlying visuospatial attention and used diffusion-weighted imaging to measure the structural properties of relevant white matter pathways.In a crossover experiment in healthy individuals, we delivered continuous theta burst TMS to the right PPC and vertex as control condition. We hypothesized that PPC inhibitory stimulation would result in a rightward visuospatial bias, decrease frontoparietal RSFC, and increase the PPC RSFC with the attentional network in the left hemisphere. We also expected that individual differences in fractional anisotropy (FA) of the frontoparietal network and the callosal pathway between the PPCs would account for variability of the TMS-induced RSFC changes.As hypothesized, TMS over the right PPC caused a rightward shift in line bisection judgment and increased RSFC between the right PPC and the left superior temporal gyrus. This effect was inversely related to FA in the posterior corpus callosum. Local inhibition of the right PPC reshapes connectivity in the attentional network and depends significantly on interhemispheric connections.

A novel Theta Burst Transcranial Magnetic Stimulation (θTMS) ‘Malta’ protocol to decrease suicidal ideation and hospital admissions – a case series

A novel Theta Burst Transcranial Magnetic Stimulation (θTMS) ‘Malta’ protocol to decrease suicidal ideation and hospital admissions – a case series

Reducing variability of perceptual decision making with offline theta-burst TMS of dorsal medial frontal cortex

BackgroundRecent evidence suggests that the dorsal medial frontal cortex (dMFC) may make an important contribution to perceptual decision-making, and not only to motor control. Objective/hypothesisBy fitting psychometric functions to behavioural data after TMS we tested whether the dMFC is critical specifically for the precision and/or bias of perceptual judgements. Additionally we aimed to disentangle potential roles of the dMFC in dealing with perceptual versus response switching. MethodsA subjective visual vertical task (SVV) was used in which participants weight visual (and other, e.g., vestibular) information to establish whether a line is oriented vertically. To ensure a high perceptual demand (putatively necessary to demonstrate a dMFC involvement) SVV lines were presented inside pop-out targets within a visual search array. Distinct features of perceptual performance were analysed before as compared to following theta-burst TMS stimulation of the dMFC, a control site, or no stimulation, in three groups, each of 20 healthy participants. ResultsdMFC stimulation improved the precision of verticality judgments. Moreover, dMFC stimulation improved accuracy, selectively when response switches occurred with perceptual repeats. ConclusionThese findings point to a causal role of the dMFC in establishing the precision of perceptual decision making, demonstrably dissociable from an additional role in motor control in attentionally demanding contexts.

Potential employment of transcranial magnetic stimulation as a beneficial intervention in children with amblyopia: a brief overview

Amblyopia is an early functional imbalance between each eye and the brain that may result in visual cortex inhibition. Current conservative treatments involve altering the input from the ‘good eye’, for example, using patching or biochemical penalization. Direct brain stimulation to the amblyopic cortex might improve the condition. This paper aimed to systematically review the published scientific literature regarding the use of transcranial magnetic stimulation (TMS) as a potential method for treatment in the amblyopic visual cortex. This study was a systematic review of the published scientific literature related to theTMS for the treatment of amblyopia that was performed using “TMS, amblyopia” as keywords. However, only three research papers were found and included in the literature review. A study showed that repetitive TMS of the visual cortex can temporarily improve contrast sensitivity in the amblyopic visual cortex. Another study used continuous thetaburst stimulation (cTBS) delivered to the visual cortex while patients viewed a high contrast stimulus with their non-amblyopic eye. It was found that daily theta burst TMS stimulation improved amblyopic eye contrast sensitivity in five adult volunteers. The TMS also increased median visual acuity in the patient with amblyopia after stimulation with no significant changes in the placebo group.Protocol employing repetitive administration of TMS might result in beneficial effects in amblyopia treatment. TMS works in brain dynamics and experience-dependent plasticity, all of which could be important in investigating and treating amblyopia.

Influence of theta-burst transcranial magnetic stimulation over the dorsolateral prefrontal cortex on emotion processing in healthy volunteers

Repetitive transcranial magnetic stimulation is a potential treatment option for depression, with the newer intermittent theta-burst stimulation (iTBS) protocols providing brief intervention. However, their mechanism of action remains unclear. We investigated the hypothesis that iTBS influences brain circuits involved in emotion processing that are also affected by antidepressants. We predicted that iTBS would lead to changes in performance on emotion-processing tasks. We investigated the effects of intermittent TBS (iTBS) over the left dorsolateral prefrontal cortex (DLPFC) on the processing of emotional information (word recall and categorization, facial emotion recognition, and decision-making) in 28 healthy volunteers by contrasting these effects with those of sham stimulation. Each volunteer received iTBS and sham stimulation in a blinded crossover design and completed the emotion-processing tasks before and after stimulation. Compared to sham stimulation, iTBS increased positive affective processing for word recall, yet had an unexpected effect on facial emotion recognition for happy and sad faces. There was no evidence of an effect on decision-making or word categorization. We found support for our hypothesis that iTBS influences emotion processing, though some changes were not in the expected direction. These findings suggest a possible common mechanism of action between iTBS and antidepressants, and a complex neural circuitry involved in emotion processing that could potentially be tapped into via brain stimulation. Future research should investigate the neural correlates of emotion processing more closely to inform future iTBS protocols.

Obesity is Associated with Reduced Plasticity of the Human Motor Cortex.

Obesity is characterised by excessive body fat and is associated with several detrimental health conditions, including cardiovascular disease and diabetes. There is some evidence that people who are obese have structural and functional brain alterations and cognitive deficits. It may be that these neurophysiological and behavioural consequences are underpinned by altered plasticity. This study investigated the relationship between obesity and plasticity of the motor cortex in people who were considered obese (n = 14, nine males, aged 35.4 ± 14.3 years) or healthy weight (n = 16, seven males, aged 26.3 ± 8.5 years). A brain stimulation protocol known as continuous theta burst transcranial magnetic stimulation was applied to the motor cortex to induce a brief suppression of cortical excitability. The suppression of cortical excitability was quantified using single-pulse transcranial magnetic stimulation to record and measure the amplitude of the motor evoked potential in a peripheral hand muscle. Therefore, the magnitude of suppression of the motor evoked potential by continuous theta burst stimulation was used as a measure of the capacity for plasticity of the motor cortex. Our results demonstrate that the healthy-weight group had a significant suppression of cortical excitability following continuous theta burst stimulation (cTBS), but there was no change in excitability for the obese group. Comparing the response to cTBS between groups demonstrated that there was an impaired plasticity response for the obese group when compared to the healthy-weight group. This might suggest that the capacity for plasticity is reduced in people who are obese. Given the importance of plasticity for human behaviour, our results add further emphasis to the potentially detrimental health effects of obesity.

Evidence for Immediate Enhancement of Hippocampal Memory Encoding by Network-Targeted Theta-Burst Stimulation during Concurrent fMRI.

The hippocampus supports episodic memory via interaction with a distributed brain network. Previous experiments using network-targeted noninvasive brain stimulation have identified episodic memory enhancements and modulation of activity within the hippocampal network. However, mechanistic insights were limited because these effects were measured long after stimulation and therefore could have reflected various neuroplastic aftereffects with extended time courses. In this experiment with human subjects of both sexes, we tested for immediate stimulation impact on encoding-related activity of the hippocampus and immediately adjacent medial-temporal cortex by delivering theta-burst transcranial magnetic stimulation (TBS) concurrent with fMRI, as an immediate impact of stimulation would suggest an influence on neural activity. We reasoned that TBS would be particularly effective for influencing the hippocampus because rhythmic neural activity in the theta band is associated with hippocampal memory processing. First, we demonstrated that it is possible to obtain robust fMRI correlates of task-related activity during concurrent TBS. We then identified immediate effects of TBS on encoding of visual scenes. Brief volleys of TBS targeting the hippocampal network increased activity of the targeted (left) hippocampus during scene encoding and increased subsequent recollection. Stimulation did not influence activity during an intermixed numerical task with no memory demand. Control conditions using beta band and out-of-network stimulation also did not influence hippocampal activity or recollection. TBS targeting the hippocampal network therefore immediately impacted hippocampal memory processing. This suggests direct, beneficial influence of stimulation on hippocampal neural activity related to memory and supports the role of theta-band activity in human episodic memory.SIGNIFICANCE STATEMENT Can noninvasive stimulation directly impact function of indirect, deep-brain targets, such as the hippocampus? We tested this by targeting an accessible region of the hippocampal network via transcranial magnetic stimulation during concurrent fMRI. We reasoned that theta-burst stimulation would be particularly effective for impacting hippocampal function, as this stimulation rhythm should resonate with the endogenous theta-nested-gamma activity prominent in hippocampus. Indeed, theta-burst stimulation targeting the hippocampal network immediately impacted hippocampal activity during encoding, improving memory formation as indicated by enhanced later recollection. Rhythm- and location-control stimulation conditions had no such effects. These findings suggest a direct influence of noninvasive stimulation on hippocampal neural activity and highlight that the theta-burst rhythm is relatively privileged in its ability to influence hippocampal memory function.

Causal Contribution of Awake Post-encoding Processes to Episodic Memory Consolidation

Stable representations of past experience are thought to depend on processes that unfold after events are initially encoded into memory. Post-encoding reactivation and hippocampal-cortical interactions are leading candidate mechanisms thought to support memory retention and stabilization across hippocampal-cortical networks. Although putative consolidation mechanisms have been observed during sleep and periods of awake rest, the direct causal contribution of awake consolidation mechanisms to later behavior is unclear, especially in humans. Moreover, it has been argued that observations of putative consolidation processes are epiphenomenal and not causally important, yet there are few tools to test the functional contribution of these mechanisms in humans. Here, we combined transcranial magnetic stimulation (TMS) and fMRI to test the role of awake consolidation processes by targeting hippocampal interactions with lateral occipital cortex (LOC). We applied theta-burst TMS to LOC (and a control site) to interfere with an extended window (approximately 30-50min) after memory encoding. Behaviorally, post-encoding TMS to LOC selectively impaired associative memory retention compared to multiple control conditions. In the control TMS condition, we replicated prior reports of post-encoding reactivation and memory-related hippocampal-LOC interactions during periods of awake rest using fMRI. However, post-encoding LOC TMS reduced these processes, such that post-encoding reactivation in LOC and memory-related hippocampal-LOC functional connectivity were no longer present. By targeting and manipulating post-encoding neural processes, these findings highlight the direct contribution of awake time periods to episodic memory consolidation. This combined TMS-fMRI approach provides an opportunity for causal manipulations of human memory consolidation.

Role of the somatosensory cortex in motor memory consolidation.

Motor memories become resistant to interference by the process of consolidation, which leads to long-term retention. Studies have shown involvement of the somatosensory cortex in motor learning-related plasticity, but not directly in motor memory consolidation. This Neuro Forum article reviews evidence from a continuous theta-burst transcranial magnetic stimulation (cTBS) study by Kumar and colleagues (Kumar N, Manning TF, Ostry DJ. PLoS Biol 17: e3000469, 2019) that demonstrates the role of somatosensory, rather than motor, cortex in human motor memory consolidation during implicit motor learning.

Changes in functional connectivity after theta-burst transcranial magnetic stimulation for post-traumatic stress disorder: a machine-learning study

Intermittent theta burst stimulation (iTBS) is a novel treatment approach for post-traumatic stress disorder (PTSD), and recent neuroimaging work indicates that functional connectivity profiles may be able to identify those most likely to respond. However, prior work has relied on functional magnetic resonance imaging, which is expensive and difficult to scale. Alternatively, electroencephalography (EEG) represents a different approach that may be easier to implement in clinical practice. To this end, we acquired an 8-channel resting-state EEG signal on participants before (n = 47) and after (n = 43) randomized controlled trial of iTBS for PTSD (ten sessions, delivered at 80% of motor threshold, 1,800 pulses, to the right dorsolateral prefrontal cortex). We used a cross-validated support vector machine (SVM) to track changes in EEG functional connectivity after verum iTBS stimulation. We found that an SVM classifier was able to successfully separate patients who received active treatment vs. sham treatment, with statistically significant findings in the Delta band (1–4 Hz, p = 0.002). Using Delta coherence, the classifier was 75.0% accurate in detecting sham vs. active iTBS, and observed changes represented an increase in functional connectivity between midline central/occipital and a decrease between frontal and central regions. The primary limitations of this work are the sparse electrode system and a modest sample size. Our findings raise the possibility that EEG and machine learning may be combined to provide a window into mechanisms of action of TMS, with the potential that these approaches can inform the development of individualized treatment methods.

High-frequency versus theta burst transcranial magnetic stimulation for the treatment of poststroke cognitive impairment in humans

Because the reliability of repetitive transcranial magnetic stimulation (rTMS) in treating poststroke cognitive impairment has not been convincingly demonstrated, we systematically examined the effectiveness of this regimen with 2 protocols. We randomly allocated 41 patients with poststroke cognitive impairment to receive 5 Hz rTMS (n = 11), intermittent theta burst stimulation (iTBS; n = 15) or sham stimulation (n = 15). Each group received 10 stimulation sessions over the left dorsolateral prefrontal cortex. We performed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Beck Depression Inventory at baseline and after the intervention. The 5 Hz rTMS group showed significantly greater improvement than the sham group in RBANS total score (p = 0.006), attention (p = 0.001) and delayed memory (p < 0.001). The iTBS group showed significantly greater improvement than the sham group in RBANS total score (p = 0.005) and delayed memory (p = 0.007). The 5 Hz rTMS group exhibited a superior modulating effect in attention compared to the iTBS group (p = 0.016). Patients without comorbid hypertension (p = 0.008) were predisposed to favourable therapeutic outcomes. Although we included only patients with left hemispheric stroke, heterogeneity associated with cortical and subcortical implications existed. We did not investigate the remote effects of rTMS. Our results demonstrated that both 5 Hz rTMS and iTBS were effective for poststroke cognitive impairment in terms of global cognition, attention and memory function; the domain of attention was susceptible to 5 Hz modulation. Treatment with 5 Hz rTMS may slow cognitive decline, representing both a pivotal process in poststroke cognitive impairment and an aspect of neuroplasticity that contributes to disease-modifying strategies. NCT02006615; clinicaltrials.gov/ct2/show/NCT02006615.

Connectivity guided theta burst transcranial magnetic stimulation versus repetitive transcranial magnetic stimulation for treatment-resistant moderate to severe depression: study protocol for a randomised double-blind controlled trial (BRIGhTMIND)

IntroductionThe BRIGhTMIND study aims to determine the clinical effectiveness, cost-effectiveness and mechanism of action of connectivity guided intermittent theta burst stimulation (cgiTBS) versus standard repetitive transcranial magnetic stimulation (rTMS) in...

The role of the inferior parietal lobule in writer's cramp.

Humans have a distinguishing ability for fine motor control that is subserved by a highly evolved cortico-motor neuronal network. The acquisition of a particular motor skill involves a long series of practice movements, trial and error, adjustment and refinement. At the cortical level, this acquisition begins in the parieto-temporal sensory regions and is subsequently consolidated and stratified in the premotor-motor cortex. Task-specific dystonia can be viewed as a corruption or loss of motor control confined to a single motor skill. Using a multimodal experimental approach combining neuroimaging and non-invasive brain stimulation, we explored interactions between the principal nodes of the fine motor control network in patients with writer's cramp and healthy matched controls. Patients and healthy volunteers underwent clinical assessment, diffusion-weighted MRI for tractography, and functional MRI during a finger tapping task. Activation maps from the task-functional MRI scans were used for target selection and neuro-navigation of the transcranial magnetic stimulation. Single- and double-pulse TMS evaluation included measurement of the input-output recruitment curve, cortical silent period, and amplitude of the motor evoked potentials conditioned by cortico-cortical interactions between premotor ventral (PMv)-motor cortex (M1), anterior inferior parietal lobule (aIPL)-M1, and dorsal inferior parietal lobule (dIPL)-M1 before and after inducing a long term depression-like plastic change to dIPL node with continuous theta-burst transcranial magnetic stimulation in a randomized, sham-controlled design. Baseline dIPL-M1 and aIPL-M1 cortico-cortical interactions were facilitatory and inhibitory, respectively, in healthy volunteers, whereas the interactions were converse and significantly different in writer's cramp. Baseline PMv-M1 interactions were inhibitory and similar between the groups. The dIPL-PMv resting state functional connectivity was increased in patients compared to controls, but no differences in structural connectivity between the nodes were observed. Cortical silent period was significantly prolonged in writer's cramp. Making a long term depression-like plastic change to dIPL node transformed the aIPL-M1 interaction to inhibitory (similar to healthy volunteers) and cancelled the PMv-M1 inhibition only in the writer's cramp group. These findings suggest that the parietal multimodal sensory association region could have an aberrant downstream influence on the fine motor control network in writer's cramp, which could be artificially restored to its normal function.